Autoreactive CD4+ T cells are required for full expression of disease in human systemic lupus erythematosus and in spontaneous murine lupus. However, the Ag specificity of these CD4+ T cells remains largely unknown. Rheumatoid factor (RF) B cells function as highly efficient APCs by taking up immune complexes (IC) and presenting IC constituents to T cells. We hypothesized that Ag-specific CD4+ T cells in lupus-prone mice could be identified by stimulating the CD4+ T cells with RF B cells from AM14 RF BCR transgenic mice pulsed with IC containing lupus-associated autoantibodies and autoantigens. This approach identified several independent T cell lines that proliferated robustly in response to IC-pulsed spleen cells from the AM14 RF BCR transgenic mice. However, these T cells did not recognize an IC constituent. Instead, these T cells recognized a determinant dependent on the inheritance of the transgene-encoded Vkappa8 L chain, most likely a neoantigen created by the insertion of the transgene into the genome. Additionally, although the precise nature of the neoantigen is not known, the T cells described in this report may provide a useful tool for examining the role of T cells in the RF autoantibody response.